BG104605A - Антагонисти на рецептора на интегрин - Google Patents
Антагонисти на рецептора на интегрин Download PDFInfo
- Publication number
- BG104605A BG104605A BG104605A BG10460500A BG104605A BG 104605 A BG104605 A BG 104605A BG 104605 A BG104605 A BG 104605A BG 10460500 A BG10460500 A BG 10460500A BG 104605 A BG104605 A BG 104605A
- Authority
- BG
- Bulgaria
- Prior art keywords
- alkyl
- naphthyridin
- aryl
- tetrahydro
- acid
- Prior art date
Links
- 229940127449 Integrin Receptor Antagonists Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- 239000005557 antagonist Substances 0.000 claims abstract description 34
- 102000006495 integrins Human genes 0.000 claims abstract description 33
- 108010044426 integrins Proteins 0.000 claims abstract description 33
- 208000006386 Bone Resorption Diseases 0.000 claims abstract description 31
- 230000024279 bone resorption Effects 0.000 claims abstract description 31
- 201000010099 disease Diseases 0.000 claims abstract description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 230000033115 angiogenesis Effects 0.000 claims abstract description 24
- 230000004054 inflammatory process Effects 0.000 claims abstract description 22
- 230000004614 tumor growth Effects 0.000 claims abstract description 22
- 206010061218 Inflammation Diseases 0.000 claims abstract description 21
- 206010027476 Metastases Diseases 0.000 claims abstract description 20
- 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 19
- 230000003612 virological effect Effects 0.000 claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 16
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 16
- 208000037803 restenosis Diseases 0.000 claims abstract description 16
- 230000029663 wound healing Effects 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 557
- -1 aminosulfonyl amino Chemical group 0.000 claims description 297
- 125000003118 aryl group Chemical group 0.000 claims description 268
- 239000002253 acid Substances 0.000 claims description 154
- 239000000203 mixture Substances 0.000 claims description 130
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 65
- 125000001424 substituent group Chemical group 0.000 claims description 61
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 60
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 55
- 229910052799 carbon Inorganic materials 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 53
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 52
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 43
- 150000002148 esters Chemical class 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- 230000000694 effects Effects 0.000 claims description 38
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 37
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 31
- 241000124008 Mammalia Species 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 25
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 22
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 20
- 230000005764 inhibitory process Effects 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 19
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 16
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 16
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 16
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 16
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 16
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 14
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 14
- 229940044551 receptor antagonist Drugs 0.000 claims description 14
- 239000002464 receptor antagonist Substances 0.000 claims description 14
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 11
- 230000008485 antagonism Effects 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 230000009977 dual effect Effects 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 235000019260 propionic acid Nutrition 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 229940122361 Bisphosphonate Drugs 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 9
- 125000005605 benzo group Chemical group 0.000 claims description 9
- 150000004663 bisphosphonates Chemical class 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 9
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 9
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 8
- 125000004442 acylamino group Chemical group 0.000 claims description 8
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 239000007789 gas Substances 0.000 claims description 8
- 230000003042 antagnostic effect Effects 0.000 claims description 7
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 7
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 7
- 125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 7
- 125000003367 polycyclic group Polymers 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 6
- 239000000470 constituent Substances 0.000 claims description 6
- 239000002834 estrogen receptor modulator Substances 0.000 claims description 6
- 230000030991 negative regulation of bone resorption Effects 0.000 claims description 6
- 229940122156 Cathepsin K inhibitor Drugs 0.000 claims description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
- 230000001028 anti-proliverative effect Effects 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 231100000433 cytotoxic Toxicity 0.000 claims description 5
- 230000001472 cytotoxic effect Effects 0.000 claims description 5
- 239000003102 growth factor Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- RIKMIRIGKQJWJN-NTISSMGPSA-N (2s)-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]-2-(thiophen-2-ylsulfonylamino)propanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CNC(=O)CCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1=CC=CS1 RIKMIRIGKQJWJN-NTISSMGPSA-N 0.000 claims description 4
- DSVRSYVZAMHQET-QFIPXVFZSA-N (3s)-3-quinolin-3-yl-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound C1=CC=CC2=CC([C@@H](NC(=O)CCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 DSVRSYVZAMHQET-QFIPXVFZSA-N 0.000 claims description 4
- KZBTVXATUSKCMJ-IBGZPJMESA-N C1=CC=C2C(=C1)C=C(C=N2)[C@H](CC(=O)O)NC(=O)CCCCC3=CC(=NC=C3)N Chemical compound C1=CC=C2C(=C1)C=C(C=N2)[C@H](CC(=O)O)NC(=O)CCCCC3=CC(=NC=C3)N KZBTVXATUSKCMJ-IBGZPJMESA-N 0.000 claims description 4
- 229940124226 Farnesyltransferase inhibitor Drugs 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 4
- JEFVGZNNIIERNY-LJQANCHMSA-N (2R)-2-(2,3-dihydrofuro[3,2-b]pyridin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@H](CCCCCCCc1ccc2CCCNc2n1)c1ccc2OCCc2n1 JEFVGZNNIIERNY-LJQANCHMSA-N 0.000 claims description 3
- YUGIIBOBDNRWTQ-QFIPXVFZSA-N (2S)-2-(2,3-dihydro-1-benzofuran-6-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCCCCCCc1ccc2CCCNc2n1)c1ccc2CCOc2c1 YUGIIBOBDNRWTQ-QFIPXVFZSA-N 0.000 claims description 3
- CKGFMJYHOUFPQR-NRFANRHFSA-N (2S)-2-(2,3-dihydrofuro[2,3-b]pyridin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound O1CCC=2C1=NC=C(C=2)[C@@H](C(=O)O)CCCCCCCC1=NC=2NCCCC=2C=C1 CKGFMJYHOUFPQR-NRFANRHFSA-N 0.000 claims description 3
- JEFVGZNNIIERNY-IBGZPJMESA-N (2S)-2-(2,3-dihydrofuro[3,2-b]pyridin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCCCCCCc1ccc2CCCNc2n1)c1ccc2OCCc2n1 JEFVGZNNIIERNY-IBGZPJMESA-N 0.000 claims description 3
- UWXJYOVNXNAYOU-FYZYNONXSA-N (2s)-2-(benzenesulfonamido)-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CNC(=O)CCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1=CC=CC=C1 UWXJYOVNXNAYOU-FYZYNONXSA-N 0.000 claims description 3
- KLWNZLIFUDCWEC-FQEVSTJZSA-N (2s)-2-(benzenesulfonamido)-8-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)octanoic acid Chemical compound N([C@@H](CCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1=CC=CC=C1 KLWNZLIFUDCWEC-FQEVSTJZSA-N 0.000 claims description 3
- MFQYADPOLMPVJP-UHFFFAOYSA-N 7-[acetyl(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethyl)amino]-3-quinolin-3-ylheptanoic acid Chemical compound C1CCNC2=NC(CN(CCCCC(CC(O)=O)C=3C=C4C=CC=CC4=NC=3)C(=O)C)=CC=C21 MFQYADPOLMPVJP-UHFFFAOYSA-N 0.000 claims description 3
- 240000008564 Boehmeria nivea Species 0.000 claims description 3
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims description 3
- 101100481404 Danio rerio tie1 gene Proteins 0.000 claims description 3
- 101100481408 Danio rerio tie2 gene Proteins 0.000 claims description 3
- 229940122091 Geranylgeranyltransferase inhibitor Drugs 0.000 claims description 3
- 101710170181 Metalloproteinase inhibitor Proteins 0.000 claims description 3
- 101100481410 Mus musculus Tek gene Proteins 0.000 claims description 3
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 claims description 3
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 claims description 3
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 3
- DCSBSVSZJRSITC-UHFFFAOYSA-M alendronate sodium trihydrate Chemical compound O.O.O.[Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O DCSBSVSZJRSITC-UHFFFAOYSA-M 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 210000002950 fibroblast Anatomy 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 239000003475 metalloproteinase inhibitor Substances 0.000 claims description 3
- 229940126170 metalloproteinase inhibitor Drugs 0.000 claims description 3
- 239000002525 vasculotropin inhibitor Substances 0.000 claims description 3
- KJHPWLBZAADRMA-OAQYLSRUSA-N (2S)-2-(1-benzothiophen-2-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@H](CCCCCCCc1ccc2CCCNc2n1)c1cc2ccccc2s1 KJHPWLBZAADRMA-OAQYLSRUSA-N 0.000 claims description 2
- KJHPWLBZAADRMA-NRFANRHFSA-N (2r)-2-(1-benzothiophen-2-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=C2SC([C@H](CCCCCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CC2=C1 KJHPWLBZAADRMA-NRFANRHFSA-N 0.000 claims description 2
- UYWSQCADRBUDJY-QGZVFWFLSA-N (2s)-2-(3-fluorophenyl)-3-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylamino)butanoylamino]propanoic acid Chemical compound C1([C@@H](CNC(=O)CCCNC=2N=C3NCCCC3=CC=2)C(=O)O)=CC=CC(F)=C1 UYWSQCADRBUDJY-QGZVFWFLSA-N 0.000 claims description 2
- BECORCOXZFLCKV-IBGZPJMESA-N (2s)-2-(6-aminopyridin-3-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(N)=CC=C1[C@@H](C(O)=O)CCCCCCCC1=CC=C(CCCN2)C2=N1 BECORCOXZFLCKV-IBGZPJMESA-N 0.000 claims description 2
- WCPGJSACNAWSRU-FTBISJDPSA-N (2s)-2-(cyclohexylmethylsulfonylamino)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid;hydrochloride Chemical compound Cl.N([C@@H](CCCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)CC1CCCCC1 WCPGJSACNAWSRU-FTBISJDPSA-N 0.000 claims description 2
- PTIWTEDGDUGIHR-BOXHHOBZSA-N (2s)-2-(cyclohexylsulfonylamino)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid;hydrochloride Chemical compound Cl.N([C@@H](CCCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1CCCCC1 PTIWTEDGDUGIHR-BOXHHOBZSA-N 0.000 claims description 2
- PRKNXIWQQALQDX-AWEZNQCLSA-N (2s)-2-(methanesulfonamido)-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound C1CCNC2=NC(CCCCC(=O)NC[C@H](NS(=O)(=O)C)C(O)=O)=CC=C21 PRKNXIWQQALQDX-AWEZNQCLSA-N 0.000 claims description 2
- CGUMENUMQZYHLN-QFIPXVFZSA-N (2s)-2-[(2-phenylacetyl)amino]-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N([C@@H](CCCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)C(=O)CC1=CC=CC=C1 CGUMENUMQZYHLN-QFIPXVFZSA-N 0.000 claims description 2
- CIPHVAAOCRJYHM-SFHVURJKSA-N (3s)-3-(3-fluorophenyl)-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propylcarbamoylamino]propanoic acid Chemical compound C1([C@@H](NC(=O)NCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=CC=CC(F)=C1 CIPHVAAOCRJYHM-SFHVURJKSA-N 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- ATKOUZSQSNFNTB-UHFFFAOYSA-N 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1CCNC2=NC(C(C(O)=O)CCCCCCC)=CC=C21 ATKOUZSQSNFNTB-UHFFFAOYSA-N 0.000 claims description 2
- ZZIXZGZHBBXCPU-UHFFFAOYSA-N 3-(1-benzothiophen-2-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=C2SC(C(CCCCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CC2=C1 ZZIXZGZHBBXCPU-UHFFFAOYSA-N 0.000 claims description 2
- TTYARQCRPOCQHN-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-6-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)non-4-enoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2CCOC2=CC(C(C=CCCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 TTYARQCRPOCQHN-UHFFFAOYSA-N 0.000 claims description 2
- XBHBFRSVZRSVIA-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-6-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2CCOC2=CC(C(CCCCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 XBHBFRSVZRSVIA-UHFFFAOYSA-N 0.000 claims description 2
- GZALUXHKODWSSP-UHFFFAOYSA-N 3-(2,3-dihydrofuro[2,3-b]pyridin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N1=C2OCCC2=CC(C(CCCCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 GZALUXHKODWSSP-UHFFFAOYSA-N 0.000 claims description 2
- ASZOUZVUOPXKBN-UHFFFAOYSA-N 3-(2,3-dihydrofuro[3,2-b]pyridin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2OCCC2=NC(C(CCCCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 ASZOUZVUOPXKBN-UHFFFAOYSA-N 0.000 claims description 2
- IHBLNGBIQLIMQX-UHFFFAOYSA-N 3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound C1CCNC2=NC(CCCCC(=O)NCCC(=O)O)=CC=C21 IHBLNGBIQLIMQX-UHFFFAOYSA-N 0.000 claims description 2
- FPXFFAVXMMSMIY-UHFFFAOYSA-N 3-phenyl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C=1C=C2CCCNC2=NC=1CCCCCCC(CC(=O)O)C1=CC=CC=C1 FPXFFAVXMMSMIY-UHFFFAOYSA-N 0.000 claims description 2
- DQAGCJGRBMOXQQ-UHFFFAOYSA-N 3-pyridin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C=1C=C2CCCNC2=NC=1CCCCCCC(CC(=O)O)C1=CC=CN=C1 DQAGCJGRBMOXQQ-UHFFFAOYSA-N 0.000 claims description 2
- YBFKWPJDYFKQMV-UHFFFAOYSA-N 3-quinolin-3-yl-3-[6-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hexanoylamino]propanoic acid Chemical compound C1=CC=CC2=CC(C(NC(=O)CCCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 YBFKWPJDYFKQMV-UHFFFAOYSA-N 0.000 claims description 2
- KQJRVLULCJERGE-UHFFFAOYSA-N 3-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC(C(CCCCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 KQJRVLULCJERGE-UHFFFAOYSA-N 0.000 claims description 2
- BEBXXVDCHHRFIA-UHFFFAOYSA-N 7-(1,2,3,4,6,7,8,9-octahydrobenzo[b][1,8]naphthyridin-8-yl)-3-quinolin-3-ylheptanoic acid Chemical compound C1=CC=CC2=CC(C(CCCCC3CC4=NC=5NCCCC=5C=C4CC3)CC(=O)O)=CN=C21 BEBXXVDCHHRFIA-UHFFFAOYSA-N 0.000 claims description 2
- WLLGDCBGYWAWAY-UHFFFAOYSA-N 7-[methylsulfonyl(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethyl)amino]-3-quinolin-3-ylheptanoic acid Chemical compound C1CCNC2=NC(CN(CCCCC(CC(O)=O)C=3C=C4C=CC=CC4=NC=3)S(=O)(=O)C)=CC=C21 WLLGDCBGYWAWAY-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
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- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/08—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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Applications Claiming Priority (6)
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| US6989997P | 1997-12-17 | 1997-12-17 | |
| GBGB9807382.8A GB9807382D0 (en) | 1998-04-06 | 1998-04-06 | Vitronectin receptor antagonists |
| US8320998P | 1998-04-27 | 1998-04-27 | |
| GBGB9811295.6A GB9811295D0 (en) | 1998-05-26 | 1998-05-26 | Vitronectin receptor antagonists |
| US9262298P | 1998-07-13 | 1998-07-13 | |
| PCT/US1998/026484 WO1999031061A1 (en) | 1997-12-17 | 1998-12-14 | Integrin receptor antagonists |
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| KR (1) | KR20010033248A (de) |
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| US6521626B1 (en) | 1998-03-24 | 2003-02-18 | Celltech R&D Limited | Thiocarboxamide derivatives |
| DE69939165D1 (de) * | 1998-04-16 | 2008-09-04 | Encysive Pharmaceuticals Inc | N,n-disubstituierte amide welche die bindung von integrinen an ihre rezeptoren hemmen |
| GB9814414D0 (en) | 1998-07-03 | 1998-09-02 | Celltech Therapeutics Ltd | Chemical compounds |
| WO2000009503A1 (en) * | 1998-08-13 | 2000-02-24 | Merck & Co., Inc. | Integrin receptor antagonists |
| GB9821061D0 (en) | 1998-09-28 | 1998-11-18 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9826174D0 (en) | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
| US6518283B1 (en) | 1999-05-28 | 2003-02-11 | Celltech R&D Limited | Squaric acid derivatives |
| PT1187592E (pt) | 1999-06-02 | 2007-10-19 | Merck & Co Inc | Antagonistas dos receptores de integrina alfa v |
| US6534513B1 (en) | 1999-09-29 | 2003-03-18 | Celltech R&D Limited | Phenylalkanoic acid derivatives |
| EP1229910A4 (de) | 1999-10-04 | 2003-10-01 | Merck & Co Inc | Integrinrezeptorantagonisten |
| EP1227847A2 (de) * | 1999-10-06 | 2002-08-07 | Basf Aktiengesellschaft | Inhibitoren von endothelin-vermittelte signaltransduktionswegen und integrin alphavbeta3 rezeptorantagonisten für die kombinationstherapie |
| US6407241B1 (en) | 1999-11-08 | 2002-06-18 | Merck & Co., Inc. | Process and intermediates for the preparation of imidazolidinone αv integrin antagonists |
| GB2356630A (en) | 1999-11-10 | 2001-05-30 | Merck & Co Inc | Intermediates used in the preparation of tetrahydronaphthyridine |
| AU768875B2 (en) | 1999-11-23 | 2004-01-08 | Merck Sharp & Dohme Corp. | Process and intermediates to a tetrahydro-(1,8)-naphthyridine |
| US6455539B2 (en) | 1999-12-23 | 2002-09-24 | Celltech R&D Limited | Squaric acid derivates |
| EP1254116A4 (de) | 2000-01-24 | 2003-04-23 | Merck & Co Inc | Alpha v integrin-rezeptor antagonisten |
| AU2001248553A1 (en) | 2000-04-17 | 2001-10-30 | Celltech R And D Limited | Enamine derivatives as cell adhesion molecules |
| US6545013B2 (en) | 2000-05-30 | 2003-04-08 | Celltech R&D Limited | 2,7-naphthyridine derivatives |
| US6403608B1 (en) | 2000-05-30 | 2002-06-11 | Celltech R&D, Ltd. | 3-Substituted isoquinolin-1-yl derivatives |
| WO2002004426A1 (en) | 2000-07-07 | 2002-01-17 | Celltech R & D Limited | Squaric acid derivatives containing a bicyclic heteroaromatic ring as integrin antagonists |
| EP1305291A1 (de) | 2000-08-02 | 2003-05-02 | Celltech R&D Limited | 3-substituierte isochinolin-1-yl-derivate |
| AU2001290772A1 (en) * | 2000-09-14 | 2002-03-26 | Merck And Co., Inc. | Alpha v integrin receptor antagonists |
| US6444680B1 (en) | 2000-11-30 | 2002-09-03 | Merck & Co., Inc. | Amine salts of an integrin receptor antagonist |
| US6764842B2 (en) | 2001-03-28 | 2004-07-20 | Merck & Co., Inc. | Enantioselective bioreduction for the preparation of integrin receptor antagonist intermediates |
| WO2002085405A2 (en) | 2001-04-24 | 2002-10-31 | Merck Patent Gmbh | COMBINATION THERAPY USING ANTI-ANGIOGENIC AGENTS AND TNF$g(a) |
| PE20030120A1 (es) | 2001-06-19 | 2003-02-12 | Merck & Co Inc | Sal amina de un antagonista de receptor de integrin |
| US20040224986A1 (en) | 2002-08-16 | 2004-11-11 | Bart De Corte | Piperidinyl targeting compounds that selectively bind integrins |
| GB0420424D0 (en) * | 2004-09-14 | 2004-10-20 | Ionix Pharmaceuticals Ltd | Therapeutic compounds |
| AU2007207465B2 (en) | 2006-01-18 | 2012-12-06 | Merck Patent Gmbh | Specific therapy using integrin ligands for treating cancer |
| CN101588812A (zh) | 2007-01-18 | 2009-11-25 | 默克专利有限公司 | 使用整联蛋白配体治疗癌的特异疗法和药物 |
| CN102026671B (zh) | 2008-03-14 | 2014-09-03 | Visen医药公司 | 整联蛋白靶向试剂及使用其的体内和体外成像方法 |
| NZ597339A (en) | 2009-05-25 | 2013-10-25 | Merck Patent Gmbh | Continuous administration of cilengitide in cancer treatments |
| PH12012501104A1 (en) * | 2009-12-04 | 2014-10-14 | Nissan Chemical Ind Ltd | 2-pyridone compounds |
| US8901144B2 (en) | 2013-02-07 | 2014-12-02 | Scifluor Life Sciences, Llc | Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives |
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-
1998
- 1998-12-14 ES ES98963136T patent/ES2241192T3/es not_active Expired - Lifetime
- 1998-12-14 JP JP2000538988A patent/JP3585839B2/ja not_active Expired - Fee Related
- 1998-12-14 CA CA002315220A patent/CA2315220C/en not_active Expired - Fee Related
- 1998-12-14 HU HU0100397A patent/HUP0100397A3/hu unknown
- 1998-12-14 NZ NZ504893A patent/NZ504893A/xx unknown
- 1998-12-14 EA EA200000660A patent/EA002822B1/ru not_active IP Right Cessation
- 1998-12-14 DE DE69829996T patent/DE69829996T2/de not_active Expired - Fee Related
- 1998-12-14 EE EEP200000362A patent/EE200000362A/xx unknown
- 1998-12-14 KR KR1020007006677A patent/KR20010033248A/ko not_active Ceased
- 1998-12-14 CN CN98813567A patent/CN1284944A/zh active Pending
- 1998-12-14 IL IL13649598A patent/IL136495A0/xx unknown
- 1998-12-14 TR TR2000/02557T patent/TR200002557T2/xx unknown
- 1998-12-14 ID IDW20001164A patent/ID24955A/id unknown
- 1998-12-14 AT AT98963136T patent/ATE294163T1/de not_active IP Right Cessation
- 1998-12-14 PL PL98341215A patent/PL341215A1/xx unknown
- 1998-12-14 SK SK919-2000A patent/SK9192000A3/sk unknown
- 1998-12-14 HR HR20000401A patent/HRP20000401A2/hr not_active Application Discontinuation
- 1998-12-14 GE GEAP19985463A patent/GEP20032921B/en unknown
- 1998-12-14 AU AU18220/99A patent/AU739811B2/en not_active Ceased
- 1998-12-14 EP EP98963136A patent/EP1040098B1/de not_active Expired - Lifetime
- 1998-12-14 BR BR9813769-7A patent/BR9813769A/pt not_active IP Right Cessation
- 1998-12-14 WO PCT/US1998/026484 patent/WO1999031061A1/en not_active Ceased
-
2000
- 2000-05-31 IS IS5521A patent/IS5521A/is unknown
- 2000-06-16 NO NO20003114A patent/NO20003114L/no unknown
- 2000-07-13 BG BG104605A patent/BG104605A/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GEP20032921B (en) | 2003-03-25 |
| TR200002557T2 (tr) | 2000-12-21 |
| DE69829996D1 (de) | 2005-06-02 |
| ID24955A (id) | 2000-08-31 |
| WO1999031061A1 (en) | 1999-06-24 |
| EA002822B1 (ru) | 2002-10-31 |
| AU1822099A (en) | 1999-07-05 |
| IS5521A (is) | 2000-05-31 |
| NO20003114D0 (no) | 2000-06-16 |
| CA2315220A1 (en) | 1999-06-24 |
| HRP20000401A2 (en) | 2001-12-31 |
| NZ504893A (en) | 2002-10-25 |
| SK9192000A3 (en) | 2001-03-12 |
| DE69829996T2 (de) | 2006-02-23 |
| EA200000660A1 (ru) | 2001-02-26 |
| EP1040098A4 (de) | 2002-10-30 |
| EE200000362A (et) | 2001-12-17 |
| CN1284944A (zh) | 2001-02-21 |
| PL341215A1 (en) | 2001-03-26 |
| EP1040098A1 (de) | 2000-10-04 |
| ES2241192T3 (es) | 2005-10-16 |
| ATE294163T1 (de) | 2005-05-15 |
| NO20003114L (no) | 2000-08-16 |
| BR9813769A (pt) | 2000-10-10 |
| IL136495A0 (en) | 2001-06-14 |
| HUP0100397A3 (en) | 2002-10-28 |
| KR20010033248A (ko) | 2001-04-25 |
| CA2315220C (en) | 2006-03-21 |
| JP2002508355A (ja) | 2002-03-19 |
| JP3585839B2 (ja) | 2004-11-04 |
| EP1040098B1 (de) | 2005-04-27 |
| HUP0100397A2 (hu) | 2001-09-28 |
| AU739811B2 (en) | 2001-10-18 |
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